6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression

Ma, Yuanhang; Wang, Qimeng; Yu, Kun; Fan, Xin; Xiao, Weidong; Cai, Yangyang; Xu, Pan; Yu, Min; Yang, Hua

doi:10.1016/j.cbi.2018.04.020

Cited by 29 publications

(14 citation statements)

References 43 publications

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“…AhR KO mice display developmental abnormalities which highlight the roles of the receptor in female fertility [52] , perinatal growth [18] , [31] , regulation of blood pressure, production of peripheral lymphocyte counts [31] , [32] , [53] and increased susceptibility to colitis [54] . Recently, it has been shown in a mouse model of induced-colitis, that FICZ (a high-affinity endogenous AhR ligand) prevents intestinal barrier function via AhR activation by suppressing IL-6 and claudin-2 expression [55] .…”

Section: Physiological Roles Of the Ah Receptormentioning

confidence: 99%

AhR signaling pathways and regulatory functions

et al. 2018

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Animals and humans are exposed each day to a multitude of chemicals in the air, water and food. They have developed a battery of enzymes and transporters that facilitate the biotransformation and elimination of these compounds. Moreover, a majority of these enzymes and transporters are inducible due to the activation of xenobiotic receptors which act as transcription factors for the regulation of their target genes (such as xenobiotic metabolizing enzymes, see below §4 for the AhR). These receptors include several members of the nuclear/steroid receptor family (CAR for Constitutive Androstane Receptor, PXR for Pregnane X Receptor) but also the Aryl hydrocarbon Receptor or AhR, a member of the bHLH-PAS family (basic Helix-Loop-Helix - Period/ARNT/Single minded). In addition to the regulation of xenobiotic metabolism, numerous alternative functions have been characterized for the AhR since its discovery. These alternative functions will be described in this review along with its endogenous functions as revealed by experiments performed on knock-out animals.

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Section: Physiological Roles Of the Ah Receptormentioning

confidence: 99%

AhR signaling pathways and regulatory functions

et al. 2018

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“…Similar results were obtained in another study [ 20 ], and in their comparable investigation, Zelante and coworkers demonstrated that administration of IAl (18 mg/kg daily for 12 days) to mice ameliorated DSS-induced colitis [ 48 ]. In fact, there are nine more reports that FICZ protects against bacterial infections and colitis caused by T-cell transfer, DSS or TNBS [ 29 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ], with only one study observing no protection against TNBS-induced colitis [ 12 ]. When Qiu and colleagues injected mice intraperitoneally with 0.5 µg FICZ for 6 days, IL-22-producing ILCs accumulated both in the large intestine (LI) and, especially, in the SI [ 19 ].…”

Section: The Mechanism(s) By Which Ficz Il-22 and Butyrate Promotmentioning

confidence: 99%

“…The fact that IL-22 production by ILC3s has both beneficial and deleterious effects has led several reviews to refer to IL-22 as a two-faced cytokine or a double-edged sword [ 67 , 69 , 74 , 111 ]. Under healthy conditions, IL-22 is constitutively expressed by ILC3s in the SI independently of IL-23 [ 92 , 111 ] and barely detectable in the colonic mucosa [ 91 , 104 , 135 ].…”

Section: When the Microbial Homeostasis In The Gut Is Disruptedmentioning

confidence: 99%

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

Rannug

2020

IJMS

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Ever since the 1970s, when profound immunosuppression caused by exogenous dioxin-like compounds was first observed, the involvement of the aryl hydrocarbon receptor (AHR) in immunomodulation has been the focus of considerable research interest. Today it is established that activation of this receptor by its high-affinity endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ), plays important physiological roles in maintaining epithelial barriers. In the gut lumen, the small amounts of FICZ that are produced from L-tryptophan by microbes are normally degraded rapidly by the inducible cytochrome P4501A1 (CYP1A1) enzyme. This review describes how when the metabolic clearance of FICZ is attenuated by inhibition of CYP1A1, this compound passes through the intestinal epithelium to immune cells in the lamina propria. FICZ, the level of which is thus modulated by this autoregulatory loop involving FICZ itself, the AHR and CYP1A1, plays a central role in maintaining gut homeostasis by potently up-regulating the expression of interleukin 22 (IL-22) by group 3 innate lymphoid cells (ILC3s). IL-22 stimulates various epithelial cells to produce antimicrobial peptides and mucus, thereby both strengthening the epithelial barrier against pathogenic microbes and promoting colonization by beneficial bacteria. Dietary phytochemicals stimulate this process by inhibiting CYP1A1 and causing changes in the composition of the intestinal microbiota. The activity of CYP1A1 can be increased by other microbial products, including the short-chain fatty acids, thereby accelerating clearance of FICZ. In particular, butyrate enhances both the level of the AHR and CYP1A1 activity by stimulating histone acetylation, a process involved in the daily cycle of the FICZ/AHR/CYP1A1 feedback loop. It is now of key interest to examine the potential involvement of FICZ, a major physiological activator of the AHR, in inflammatory disorders and autoimmunity.

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“…Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, and its immunoregulatory function has been highlighted recently 12 . AhR activation has been shown to improve immune homeostasis in epithelial cells, and stimulation of oral commensal bacteria can enhance its activation in oral epithelial cells 13 , 14 . NLR pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor with a key role in host defense against pathogens 15 .…”

Section: Introductionmentioning

confidence: 99%

Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

Zhong

et al. 2019

J. Appl. Oral Sci.

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Effects of 1,25-dihydroxyvitamin D 3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model Vitamin D has been known to have important regulatory functions in inflammation and immune response and shows inhibitory effects on experimental periodontitis in animal models. However, the potential mechanism has yet to be clarified. Recent studies have highlighted Aryl hydrocarbon receptor (AhR) and its downstream signaling as a crucial regulator of immune homeostasis and inflammatory regulation. Objective: This study aimed to clarify the effect of 1,25-dihydroxyvitamin D 3 (VD3) on experimental periodontitis and AhR/nuclear factor-κB (NF-κB)/NLR pyrin domain-containing 3 (NLRP3) inflammasome pathway in the gingival epithelium in a murine model. Methodology: We induced periodontitis in male C57BL/6 wild-type mice by oral inoculation of Porphyromonas gingivalis (P. gingivalis), and subsequently gave intraperitoneal VD3 injection to the mice every other day for 8 weeks. Afterwards, we examined the alveolar bone using scanning electron microscopy (SEM) and detected the gingival epithelial protein using western blot analysis and immunohistochemical staining. Results: SEM images demonstrated that alveolar bone loss was reduced in the periodontitis mouse model after VD3 supplementation. Western blot analyses and immunohistochemical staining of the gingival epithelium showed that the expression of vitamin D receptor, AhR and its downstream cytochrome P450 1A1 were enhanced upon VD3 application. Additionally, VD3 decreased NF-κB p65 phosphorylation, and NLRP3, apoptosis-associated speck-like protein, caspase-1, interleukin-1β (IL-1β) and IL-6 protein expression. Conclusions: These results implicate the alleviation of periodontitis and the alteration of AhR/NF-κB/NLRP3 inflammasome pathway by VD3 in the mouse model. The attenuation of this periodontal disease may correlate with the regulation of AhR/NF-κB/NLRP3 inflammasome pathway by VD3.

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6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression

Cited by 29 publications

References 43 publications

AhR signaling pathways and regulatory functions

AhR signaling pathways and regulatory functions

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model

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